chr9-35682350-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000378292.9(TPM2):​c.773-187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 947,914 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 13 hom. )

Consequence

TPM2
ENST00000378292.9 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.36
Variant links:
Genes affected
TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 9-35682350-G-A is Benign according to our data. Variant chr9-35682350-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205261.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00435 (662/152296) while in subpopulation NFE AF= 0.00373 (254/68016). AF 95% confidence interval is 0.00336. There are 5 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 662 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TPM2NM_001301226.2 linkuse as main transcriptc.773-187C>T intron_variant
TPM2NM_213674.1 linkuse as main transcriptc.773-187C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TPM2ENST00000378292.9 linkuse as main transcriptc.773-187C>T intron_variant 1 P07951-2
TPM2ENST00000644325.1 linkuse as main transcriptc.*358C>T 3_prime_UTR_variant 4/4
TPM2ENST00000329305.6 linkuse as main transcriptc.773-187C>T intron_variant 2 A1
TPM2ENST00000643485.1 linkuse as main transcriptn.1499C>T non_coding_transcript_exon_variant 8/8

Frequencies

GnomAD3 genomes
AF:
0.00436
AC:
663
AN:
152178
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000700
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00222
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0318
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00373
Gnomad OTH
AF:
0.00239
GnomAD4 exome
AF:
0.00353
AC:
2812
AN:
795618
Hom.:
13
Cov.:
11
AF XY:
0.00327
AC XY:
1329
AN XY:
406426
show subpopulations
Gnomad4 AFR exome
AF:
0.000492
Gnomad4 AMR exome
AF:
0.00156
Gnomad4 ASJ exome
AF:
0.000157
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000395
Gnomad4 FIN exome
AF:
0.0194
Gnomad4 NFE exome
AF:
0.00356
Gnomad4 OTH exome
AF:
0.00307
GnomAD4 genome
AF:
0.00435
AC:
662
AN:
152296
Hom.:
5
Cov.:
32
AF XY:
0.00567
AC XY:
422
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000698
Gnomad4 AMR
AF:
0.00216
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0318
Gnomad4 NFE
AF:
0.00373
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00334
Hom.:
1
Bravo
AF:
0.00240
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.12
DANN
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145114937; hg19: chr9-35682347; API